Angiotensin II-pretreated Hucmscs Attenuate Inflammation and Reverse Pulmonary Fibrosis in SD Rat Lung

Abstract Background: Pulmonary fibrosis (PF) is an irreversible disease with a poor prognosis and a serious impact on patients' health. PF is also associated with COVID-19, especially in immunocompromised people. Herein, efforts have been made to treat PF using pretreatment of human umbilical cord mesenchymal stem cells (hucMSCs) with angiotensin II (Ang II) as a novel therapeutic method. Methods: PF model of Sprague Dawley (SD) rats were established by tracheal injection of bleomycin (BLM) (5U/Kg). On day 15 after modeling, PBS, hucMSCs or hucMSCs-Ang II were injected into tail vein. On the 23rd day after modeling, samples were taken and corresponding indexes were tested.Results: Our results first showed that Ang II pretreatment induced more hucMSCs to reach the injured lung and alleviated pulmonary fibrosis. Transplantation of hucMSCs-Ang II reduced inflammatory infiltration, increased IL-10 expression and enhanced macrophage matrix-metallopeptidase-9 (MMP-9) expression for collagen degradation. Moreover, the Ang II-treated hucMSCs decreased hydroxyproline (HYP) and alpha-smooth muscle actin (α-SMA) expression in SD rats and promoted collagen and collagen fiber degradation.Conclusions: Ang II pretreatment enhanced the homing ability of hucMSCs, and hucMSCs-Ang II transplantation reversed PF by inhibiting inflammation and promoting collagen and collagen fiber degradation, promising its clinical application in the treatment of post-inflammatory PF caused by various disorders, including COVID-19 and related pneumonia.